Uroguanylin, guanylin, lymphoguanylin and bacterial enterotoxin ST are structurally related peptides that activate common guanylate cyclase signaling molecules and, via cyclic GMP (cGMP), regulate water and ion homeostasis in a variety of tissues and organs, including the gastrointestinal (GI) tract, kidneys, lung, prostate, etc. Any disruptions in water and ionic homeostasis due to reduced production of one or more of the guanylin family of peptides can potentially lead to carcinogenic and inflammatory stimuli. Recent findings that expression of uroguanylin and guanylin is dramatically reduced in polyps and colon carcinoma tissues further support the notion that these peptide hormones are important modulators or mediators of signaling pathways leading to the processes involved in carcinogenesis and inflammatory disorders. This review briefly discusses recent research findings suggesting the novel therapeutic applications of agonist peptides of guanylate cyclase-C receptor.